Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause epilepsy and focal neurological deficits, but the cellular pathology of peritumoral cortex remains poorly defined. The aims of the present study were to define the morphological changes which occur in neurons in tumor-infiltrated cerebral cortex, and to determine whether peritumoral neurons show expression of cell stress-related proteins. Archival specimens of diffuse astrocytoma (n = 28) were identified with areas of both tumor-infiltrated cortex and apparently non-infiltrated cortex. Immunohistochemistry was performed to structural neuronal proteins (MAP-2, neurofilament proteins), beta-amyloid precursor protein, growth associated protein-43 and to injury response proteins (poly(ADP-ribose) polymerase, poly(ADP-ribose), c-fos, and c-jun). Tumor-infiltrated cortex revealed neuronal loss and architectural disarray compared to non-infiltrated cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their neuritic processes showed increasing tortuosity, varicosity, fragmentation and loss, with axonal spheroid formation and dendritic beading. Poly(ADP-ribose) polymerase, poly(ADP-ribose) and c-fos were up-regulated in both infiltrated and non-infiltrated cortex, but c-jun expression was greater in areas of tumor-infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma demonstrate, therefore, a sequence of morphological alterations in their dendritic, somatic and axonal compartments, and demonstrate a cell stress response. The patterns of cellular pathology identified suggest possible mechanisms, by which neurons are damaged and eventually lost in peritumoral brain.
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PMID:Morphological changes and stress responses in neurons in cerebral cortex infiltrated by diffuse astrocytoma. 1471 40

Light damage to the retina accelerates retinal degeneration in human diseases and rodent models. Recently, the polyphenolic phytoalexin resveratrol has been shown to exert various bioactivities in addition to its classical antioxidant property. In the present study, we investigated the effect of resveratrol on light-induced retinal degeneration together with its underlying molecular mechanisms. BALB/c mice with light exposure (5000-lux white light for 3 hours) were orally pretreated with resveratrol at a dose of 50 mg/kg for 5 days. Retinal damage was evaluated by TdT-mediated dUTP nick-end labeling, outer nuclear layer morphometry, and electroretinography. Administration of resveratrol to mice with light exposure led to a significant suppression of light-induced pathological parameters, including TdT-mediated dUTP nick-end labeling-positive retinal cells, outer nuclear layer thinning, and electroretinography changes. To clarify the underlying molecular mechanisms, the nuclear translocation of activator protein-1 subunit c-fos was evaluated by enzyme-linked immunosorbent assay, and the retinal activity of sirtuin 1 was measured by deacetylase fluorometric assay. Retinal activator protein-1 activation, up-regulated following light exposure, was significantly reduced by application of resveratrol. In parallel, retinal sirtuin 1 activity, reduced in animals with light damage, was significantly augmented by resveratrol treatment. Our data suggest the potential use of resveratrol as a therapeutic agent to prevent retinal degeneration related to light damage.
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PMID:Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation. 2070 95

Exposure to light contributes to the development and progression of retinal degenerative diseases. However, the mechanisms underlying light-induced tissue damage are not fully understood. Here, we examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (angiotensin II receptor blockers; ARBs) valsartan, losartan, and candesartan before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. This effect was dose-dependent and observed across the ARB class of inhibitors. Further evaluation of valsartan showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The role of ROS in retinal pathogenesis was investigated further using the antioxidant N-acetyl-l-cysteine (NAC). Treatment of light-exposed mice with NAC before the light exposure suppressed the visual function impairment and photoreceptor cell histological changes due to apoptosis. Moreover, treatment with valsartan or NAC suppressed the induction of c-fos (a component of the AP-1 transcription factor) and the upregulation of fasl (a proapoptotic molecule whose transcript is regulated downstream of AP-1). Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural tissue damage.
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PMID:Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in the mouse retina. 2466 96